Evaluating phase II results of Baxdrostat, an aldosterone synthase inhibitor for hypertension

ABSTRACT

Introduction

Hypertension, a global health concern, poses a significant risk for other cardiovascular diseases. While lifestyle modifications and interventions like the Dietary Approaches to Stop Hypertension (DASH) diet offer some respite, their maintenance can be challenging. Recently, the spotlight has turned toward the renin-angiotensin-aldosterone system, a crucial player in the pathophysiology of hypertension. Contrary to other drugs, Baxdrostat, an innovative aldosterone synthase inhibitor (ASI), targets aldosterone synthesis, mitigating negative systemic effects.

Areas covered

Baxdrostat showcases rapid absorption, high oral bioavailability, and significant selectivity for aldosterone synthase which presents a proactive approach to hypertension management by reducing aldosterone levels. Early trials have demonstrated its potential in lowering blood pressure in resistant hypertension cases. Current clinical trials are also exploring its application in primary aldosteronism and chronic kidney disease, with preliminary findings indicating its promise as a novel antihypertensive agent. This article encapsulates the current state of knowledge regarding Baxdrostat, encompassing its uses, ongoing clinical trials, and potential future clinical applications.

Expert opinion

Future research endeavors will play a pivotal role in unveiling the effectiveness and safety profile of this novel medication. Thus, positioning the baxdrostat as a valuable addition to the armamentarium of antihypertensive agents, especially for patients with complex, multifactorial hypertensive conditions.

KEYWORDS:

• Baxdrostat
• aldosterone synthase inhibitors
• CYP11B2
• essential hypertension
• treatment-resistant hypertension
• primary hyperaldosteronism

Article highlights

• Prolonged and untreated hypertension (HTN) can lead to a variety of detrimental effects, from heart failure and myocardial infarction to systemic failure.

• The renin-angiotensin-aldosterone system is an important system that exacerbates systemic HTN via sodium and fluid retention alongside associated alterations in the functioning of the heart, peripheral vasculature, and kidneys.

• Aldosterone synthesis inhibition therefore has the potential of decreasing oxidative stress and endothelial dysfunction associated with HTN, causing more endothelial nitric oxide synthesis, release, and vasorelaxation.

• Baxdrostat is a novel drug, 100 times more selective and potent inhibitor of aldosterone synthase (AS) which reduces aldosterone synthesis and mitigates its negative effects on both receptor-mediated and non-genomic processes.

• Several phase 1 and 2 clinical trials have produced promising results. Recently, a phase 2 study of baxdrostat in treatment-resistant hypertensive patients produced dose-dependent decrease in aldosterone, systolic, and diastolic blood pressure with no cortisol effect. Baxdrostat’s selectivity and potency give it a comparative advantage over mineralocorticoid antagonists.

• Some data from phase 2 clinical trials examining the safety and efficacy of baxdrostat (CIN-107) in uncontrolled hypertension, chronic-kidney disease, and primary Aldosteronism have not yet been published. Further study in a phase 3 clinical trial is currently underway.

Declarations of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have served as a consultant for Boehringer Ingelheim, Bayer, Astra Zeneca (not baxdrfostat), Bristo; Meyers Squib, KBP Biosciences* (*stock options). They are also involved in the US Patent 9,931,412 for site-specific delivery of eplerenone to the myocardium.

Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contribution

All Co-authors consent to the submission of the manuscript. Everyone equally contributed to the success of the work appended.

Author Ayoola Awosika helped with Conceptualization, writing 1^st draft and 2^nd draft.

Co-Author Ujjal Bose helped with writing 1^st draft and 2^nd draft.

Co-Author Yoonje Cho helped with writing 1^st draft and methodology screening.

Co-author Adekunle Omole helped with writing 2^nd draft and review/editing.

Co-Author Uzochukwu Adabanya helped with methodology screening, 2^nd draft and review.

Finally, all coauthors reviewed the final manuscript for any further correction and additions to ensure integrity of the submission. Then we all approved and consented to final submission.

Additional information

Funding

This paper was not funded.